tbuckley/cabot-search huggingface dataset:
Abstract 12397: A First Case of Myocardial Infarction Due to Multisystem Inflammatory Syndrome After Sars-cov-2 Vaccination
Authors: Kenji Yanishi, Masao Takigami, Satoaki Matoba
Journal: Circulation (2022)

A 22-year-old man without any medical history developed fever three days after receiving the first dose of the Moderna vaccine (mRNA-1273; Moderna, Inc., Massachusetts, United States), but his symptom was naturally improved. On the 12th day after the second vaccination, he developed fever, headache, and redness in both eyes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction test result was negative, but his symptoms were gradually worsening. Blood examinations on admission (the 24th day after the second vaccination, Day1) showed an increasing of C-reactive protein and D-dimer. In addition, contrast-enhanced computed tomography (CT) revealed hepatosplenomegaly and a contrast-enhanced defective area in the kidney. Subsequently, his fever subsided, and he was discharged on Day23, but he was readmitted for chest pain on Day26. We diagnosed non-ST elevation myocardial infarction (MI), and coronary angiography (CAG) revealed total occlusion of the atrioventricular branch of the right coronary artery (RCA), and 90% stenotic lesions with &gt;3 mm coronary ectasia in the left circumflex artery (LCx). The optical coherence tomography (OCT) findings showed blurring of vessel construction, intimal thickening, medial destruction, and thrombus in the RCA and LCx lesions. Based on the Brighton Collaboration Network definition, we diagnosed the condition as multisystem inflammatory syndrome (MIS) after SARS-CoV-2 vaccination (MIS-V), presenting with systemic vasculitis lesions. Following antithrombotic therapy with warfarin, aspirin, and prednisolone (60mg/day), his D-dimer levels and inflammatory response promptly improved. Furthermore, coronary artery irregularities, especially in the LCx lesion, showed improvement on CAG on Day43. Follow-up OCT showed resolution of the thrombus and healing of the medial destruction. The prednisolone dose was reduced, and the patient was discharged. Follow-up CAG and OCT after six months showed further improvements of initial findings. So, we decided to stop warfarin and prednisolone according to these results. His clinical course is very good without symptoms after that. This is the first report of MI due to MIS-V with longitudinal OCT findings.
Abstract 14252: Cumulative Apolipoprotein B Blood Concentrations During Early Adulthood and Incident Atherosclerotic Cardiovascular Disease Risk After Age 40 Years: The Coronary Artery Risk Development in Young Adults Study
Authors: John T Wilkins, Hongyan Ning, Allan D Sniderman, Neil J Stone, James D Otvos, David R Jacobs, Konrad Sawicki, Konrad T Sawicki, Venkatesh L Murthy, Ravi V Shah, Norrina B Allen, Donald Lloyd-Jones
Journal: Circulation (2022)

Introduction: The associations between cumulative exposure to apolipoprotein B (apoB) containing lipoproteins across early adult life and incident ASCVD in later life have not been quantified. Methods: Of 4945 eligible Coronary Artery Risk Development in Young Adults (CARDIA) cohort participants we used NMR to measure apoB in 3110 participants who had samples available from the years 2, 7, 15, and 30 exams. To mitigate biases from missingness of data we conducted multiple imputation for apoB levels for the residual 1,835 participants without NMR measures of apoB. We estimated the participant-specific apoB throughout the exposure period (ages 19 to 40y) using nonparametric spline models. The area under the apoB/age curve was calculated as cumulative exposure and expressed in mg/dL*years. To quantify the association between cumulative apoB exposure during early life with incident ASCVD after age 40y we used demographic- and risk factor-adjusted* Cox regression models (see table). We used a restricted cubic spline to examine the pattern of association across the range of cumulative apoB exposure. Results: 4945 CARDIA participants were followed for a total of 88664 person*years; 255 incident ASCVD events occurred after age 40y. Participants with higher cumulative apoB levels were more likely to be men; and have higher BMI, BP, glucose, and tobacco use. In demographic and risk factor adjusted models a 100mg/dL*yr difference in cumulative apoB from ages 19 to 40y (representing a mean yearly difference of about +5mg/dL) was associated with HR 1.15 (95% CI:1.10-1.19) and HR 1.10 (95%CI:1.06-1.15) for ASCVD events, respectively. At apoB exposures &gt;1700mg/dL*y (&gt;80mg/dL/y) there was a strong, direct association with incident ASCVD after age 40y. Conclusion: Prevention strategies that reduce apoB exposures in early adult life will likely attenuate ASCVD risks later in life; targeting a usual apoB level &lt; 80mg/dL may provide maximal benefit.
Abstract 12187: Transcatheter versus Surgical Aortic Valve Replacement With Concurrent Coronary Revascularization: A Systematic Review and Meta-Analysis
Authors: Yosuke Sakurai, Yujiro Yokoyama, Shinichi Fukuhara, Hisato Takagi, Toshiki Kuno
Journal: Circulation (2022)

Objective: This meta-analysis aimed to evaluate outcomes of transcatheter aortic valve replacement (TAVR) with percutaneous coronary intervention (PCI) versus surgical aortic valve replacement (SAVR) with coronary artery bypass grafting (CABG). Methods: MEDLINE and EMBASE were searched through November 2021 to identify studies comparing TAVR+PCI and SAVR+CABG for severe aortic stenosis with concurrent coronary artery disease. Outcomes of interest were long-term all-cause mortality, repeat coronary intervention, rehospitalization, myocardial infarction, and stroke during follow-up, and 30-day periprocedural outcomes. Results: Two randomized controlled trials and six observational studies including a total of 104,220 patients (TAVR+PCI, n = 5,004; SAVR+CABG, n = 99,226) were included. Median follow-up periods ranged from one to three years. TAVR+PCI was associated with higher all-cause mortality and coronary reintervention during follow-up period (Hazard Ratio [HR], 1.35; 95% confidence interval [CI], 1.11-1.65; p = 0.003, HR, 4.14; 95% CI, 1.74-9.86; p = 0.001, respectively), 30-day permanent pacemaker implantation rate (Odds Ratio [OR], 3.79; 95% CI, 1.61-8.95; p = 0.002), and periprocedural vascular complications (OR 6.97; 95% CI, 1.85-26.30; p = 0.004). In contrast, TAVR+PCI was associated with a lower rate of 30-day acute kidney injury (OR, 0.32; 95% CI, 0.20-0.50; p = 0.0001). Rehospitalization, myocardial infarction, stroke during follow-up, and other periprocedural outcomes including 30-day mortality were similar in both groups. Conclusions: In patients with severe aortic stenosis and coronary artery disease, TAVR+PCI was associated with higher all-cause mortality at follow-up compared with SAVR+CABG. Heart team approach to assess TAVR candidacy remains imperative.
Abstract 13700: LncRNA <i>MERRICAL</i> Controls Macrophage Chemotaxis and Vascular Inflammation by <i>In-cis</i> Regulation of CCL3/4 via H3k4me3 in Diabetes-Associated Atherosclerosis
Authors: Jingshu Chen, Anurag Jamaiyar, Rulin Zhuang, Grasiele Sausen, Henry S. Cheng, Daniel Perez-Cremades, ASPASIA TZANI, Michael McCoy, Carmel Assa, Samuel Eley, Jorge Plutzky, Mark W Feinberg
Journal: Circulation (2022)

Introduction: Diabetes-associated atherosclerosis is characterized by excessive vascular wall inflammation, including impaired lipid deposition, increased immune cell infiltration and plaque formation in the vessel wall. Macrophages are instrumental for lesion formation, however the mechanisms underlying their impaired functional capacity remain poorly understood in diabetes. Herein, we identify a unique role of a macrophage-enriched lncRNA MERRICAL (Macrophage Enriched lncRNA Regulates Inflammation, Chemotaxis, and AtheroscLerosis) in the development of diabetes-associated atherosclerosis. Methods: Transcriptomic analysis of the aortic intima from Ldlr -/- mice was performed at 4 time points along the continuum of lesion progression and regression under a high fat, high sucrose-containing (HFSC) or chow diet, respectively, to identify differentially expressed lncRNAs. Gain- and loss-of-function cell-based assays, RNA-protein interactions, and in vivo knockdown were performed to uncover the role of a top lncRNA candidate. Results: LncRNA MERRICAL is nuclear localized and increased by 249% in intimal lesions during progression. Transcriptomic analysis of MERRICAL -deficient bone marrow-derived macrophages showed decreased chemokine and inflammatory gene expression for Ccl3, Ccl4, and Il1β, with reduced chemotaxis and inflammatory-associated gene ontology pathways. Gain- and loss-of-function studies demonstrated the role of lncRNA MERRICAL in cis -regulation of its neighboring genes Ccl3 and Ccl4, an effect that is mediated in part via interaction with the histone modification enzyme H3K4me3. Remarkably, systemic knockdown of MERRICAL in HFSC-fed mice strongly reduced lesion formation by 73% in the aortic sinus by inhibiting the pro-inflammatory and Ccl3 - and Ccl4 -associated chemotactic response and decreasing the recruitment of leukocytes into the aortic wall. Conclusions: These findings establish a cis -regulatory mechanism by which a macrophage-specific lncRNA, MERRICAL , potently inhibits pro-inflammatory and chemotactic responses to alleviate lesion progression in diabetes, with implications for a broad range of diabetes-associated vascular disease states.
Abstract 12489: Reclassification of 10-Year Coronary Heart Disease Risk in 5324 Primary Prevention Patients: Ascvd, Rrs versus Mesa-Cac Scores
Authors: Adel Hajj Ali, Michael Nakhla, Leslie Cho, Raul Seballos, Richard S Lang, Steven Feinleib, Scott D Flamm, Paul SCHOENHAGEN, Tom Kai Ming K Wang, Milind Y Desai
Journal: Circulation (2022)

Introduction: Cardiovascular (CV) risk prediction score have provided physicians with powerful screening and prevention tools. Hypothesis: In a large screening program of asymptomatic individuals, we sought to assess the CV risk reclassification provided by comparing multiethnic study on subclinical atherosclerosis-coronary artery calcium scoring (CACS) vs American Heart Association (AHA)-American College of Cardiology (ACC)-Atherosclerotic Cardiovascular Disease (ASCVD) score and Reynolds Risk Score (RRS). Methods: We included all 5324 patients (age 57± 8 years, 76% male and 87% white) who underwent CACS screening in a primary prevention clinic between 3/2016 and 10/2021. 10-year ASCVD, RRS and MESA-CACS scores were calculated and categorized as 0, 1-4.99%, 5-9.99% and ≥10%. Results: Mean MESA-CACS, ASCVD and RRS were 4.9± 5.6%, 6.6 ± 6.2%, and 4.5 ± 4.4%. A total of 2962 (56%) had a CAC of 0 of which 481 (16%) were on statin. MESA-CAC was moderately correlated with ASCVD and RRS (R= 0.65 and 0.62 respectively, both p&lt;0.001, Figure 1a-b). Compared to ASCVD score, using MESA-CACS resulted in a downgraded risk in 1666 (31%) subjects, while 738 (14%) had an upgrade in risk. Similarly, compared to RRS, using MESA-CAC resulted in an upgraded risk in 797 (15%) and a downgrade in 1380 (26%) subjects. Additionally, 916 subjects (421 and 495 with an ASVCD score between 5-7.5 and 7.5-20% respectively) met criteria for statin therapy, but had CACS of 0, of which 234 (26%) were on a statin. Conclusions: Utilization of MESA-CACS in primary prevention results insignificant reclassification of traditional CV risk scores with, RRS underestimating and ASCVD overestimating the 10 year-coronary heart disease risk. A quarter of patients with ASCVD score 5-20% who were on statins had a CACS of 0; hence CACS can potentially help refine subjects who would best benefit from statin therapy. Fig 1 Distribution of patients with %10-year risk based on MESA CAC score vs ASCVD (A) and RRS (B)
Abstract 13599: LX2020, an Adeno Associated Viral-Based Plakophilin 2 Gene Therapy Stabilizes Cardiac Disease Phenotype in a Severe Mouse Model of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Farah Sheikh, Jing Zhang, Jie Wang, William H Bradford, Anju Nair, Anthony Fargnoli, Nithya Selvan, Sonia Gutierrez, Ken Law, Tim Fenn, Paul McCormac, Jay A Barth, Richie Khanna
Journal: Circulation (2022)

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) increases risk of sudden cardiac death (SCD) and can progress to heart failure. Clinical studies have established 40-50% prevalence of mutations to desmosomal genes, with plakophilin-2 (PKP2) being the most frequent. To date, no effective treatment exists for ARVC. LX2020 is a novel AAV gene therapy that restores cardiac expression of human PKP2. A proof-of-concept study with LX2020 was conducted in a severe novel PKP2 mutant mouse model that exhibits all classic phenotypes of ARVC. Hypothesis: LX2020 mediated PKP2 expression is sufficient to scaffold the desmosomal cell-cell complex to promote survival as well as preserving cardiac electrical and mechanical function. Methods: A total of N=16 PKP2 Hom mice were randomized for vehicle/formula control (VC), low dose (LD) and high dose (HD). LX2020 was administered at postnatal day 2 and mice were analyzed 4-weeks post administration. Endpoints included survival, EKG, cardiac MRI and desmosomal levels of PKP2, desmoplakin (DSP), desmoglein-2 (DSG2), plakoglobin (JUP), along with fascia-adherens (N-Cad), and gap junction (CX43), using western blot analyses. Results: LX2020 showed dose dependent improvements in ARVC related deficits in PKP2 mice, including survival. HD resulted in 100% survival of PKP2 mutant mice, while LD resulted in 60% survival, when compared to 50% survival with VC. ECG data revealed suppression of ectopic beats in 100% of PKP2 mutant mice at HD and 75% suppression at LD when compared to 60% with VC. MRI HD improved left and right ejection fraction, as well as reduced right and left end-diastolic and systolic volumes, when compared to VC. LD showed a mild impact on left ventricular end-diastolic and end-systolic volumes like HD. Mechanistically, while LD showed limited increase in cardiac PKP2 expression, HD showed substantial cardiac PKP2 expression. Significantly increased levels of other desmosomal proteins, especially DSP and DSG2, were seen suggesting scaffolding functions to PKP2. Conclusions: These data indicate that the restoration of cardiac PKP2 expression can halt or slow ARVC disease progression, making LX2020 a promising gene therapy candidate for treating PKP2 mutation patients.
Abstract 12949: Altered Fatty Acids and Oxylipins Metabolism Differentiate Isolated Post-Capillary versus Combined Pre- and Post-Capillary Pulmonary Hypertension
Authors: Amber B Tang, Mona Alotaibi, Kari Roberts, Ioana R Preston, Rod Warburton, Mohit Jain, Susan Cheng, Nicholas Hill
Journal: Circulation (2022)

Introduction: Pulmonary hypertension due to left heart disease (Group 2) is the most common type of pulmonary hypertension and has two subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the molecular characteristics that distinguish these two subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH), as has previously been suggested. Many lipid metabolites, including a diverse group of bioactive lipid mediators known as oxylipins, have been associated with cardiovascular disease and other inflammatory conditions. Therefore, we sought to characterize oxylipin and other bioactive lipid profiles among patients with Ipc-PH and Cpc-PH, as well as those with PAH. Methods: We studied 129 patients with Ipc-PH (n=38), Cpc-PH (n=52), or PAH (n=39) between June 2006 and March 2012. Liquid chromatography-mass spectrometry was used to assess 350 lipid metabolite analytes in each patient. Results: In multivariable analyses adjusting for age, sex, BMI, and pulmonary hypertension medications, we observed 34 metabolites were significantly increased and 10 were decreased in Ipc-PH compared to Cpc-PH (Figure). Among these same metabolites, only 9 were significantly different between Cpc-PH and PAH. Compared to patients with Ipc-PH, those with Cpc-PH had elevated levels of fatty acyl esters of hydroxy fatty acids and polyunsaturated fatty acids as well as lower levels of anti-inflammatory and pulmonary vascular relaxant oxylipins. Conclusions: Overall, these findings suggest that Cpc-PH may diverge from Ipc-PH and share some molecular similarities with PAH. Identifying key molecular targets involved in Cpc-PH pathophysiology may be critical for diagnostic purposes and in the development of novel therapeutic avenues for patients with Cpc-PH.
Abstract 14104: Trends and Associated Outcomes in Neonates With Ductal-Dependent Cyanotic Congenital Heart Disease Undergoing Surgical Systemic-Pulmonary Artery Shunts versus Catheter-Based Ductal Stents From the Pediatric Health Information System Database
Authors: Eleonore Valencia, Steven Staffa, Nicola Maschietto, Michael Kuntz, Katherine Zaleski, Aditya K Kaza, Viviane Nasr
Journal: Circulation (2022)

Introduction: Neonates with ductal-dependent cyanotic congenital heart disease (CCHD) require palliation to establish stable pulmonary blood flow (PBF). Surgical systemic-to-pulmonary artery shunts have been the standard approach. More recently, catheter-based ductal stents have been performed as an alternative less invasive intervention. We aimed to characterize recent trends in the utilization of surgical shunts versus ductal stents and compare associated outcomes. Methods: Using data from the Pediatric Health Information System, we retrospectively analyzed neonates with CCHD who underwent surgical shunt or ductal stent placement to establish stable PBF between January 2016 and December 2021. Neonates with CCHD with ductal-dependent PBF were identified by ICD-10 diagnosis codes and stratified by surgical shunt or ductal stent using ICD-10 procedure codes. The primary outcome was post-intervention length of stay (LOS). Secondary outcomes were rate of reintervention on the ductal stent, surgical shunt, atrial septum, right ventricular outflow tract, or branch pulmonary arteries and adjusted hospital charges per admission. Results: Of the 931 patients included, 65.4% underwent a surgical shunt over the 5-year period. The proportion who underwent a ductal stent increased from 18.9% to 53.5% from 2016 to 2021. There was no significant difference in mortality (surgical shunt 6.1% vs ductal stent 4.4%, P=0.27). The median adjusted difference in LOS was 11 days greater for the surgical shunt cohort (95% CI: 8.5-13.5, P&lt;0.001). The likelihood of reintervention was significantly greater in the ductal stent group (30 days: adjusted OR=2.19, 95% CI: 1.02-4.71, P=0.044; 3 months: adjusted OR=4.85, 95% CI: 3.13-7.52, P&lt;0.011). Median adjusted total hospital charges were $572,400 (367,600-967,900) versus $302,500 (214,000-523,000) for the surgical shunt and ductal stent groups, respectively (P&lt;0.001). Conclusions: Ductal stenting has become an increasingly utilized palliative approach to secure PBF in neonates with CCHD across various centers in the United States. Ductal stenting is associated with decreased LOS and reduced overall charges for the index hospitalization but also with a greater reintervention rate than surgical shunting.
Abstract 13792: Different Trajectories of Specific-Disease QoL in Stroke Survivors and Their Associations With Caregiver Anxiety, Depression and Burden: A Longitudinal Study
Authors: Gianluca Pucciarelli, Davide Bartoli, Ercole Vellone, Rosaria Alvaro, Andrea Greco, Agostino Brugnera
Journal: Circulation (2022)

Introduction: Stroke symptoms often predict disability and low quality of life (QOL) in stroke survivors. Stroke survivors’ QOL could have an influence on their caregivers’ variables, such as anxiety, depression or burden and consequently caregivers’ QOL. Hypothesis: The aims of this study were to: 1) identify the distinct trajectories of the stroke specific QoLs in stroke survivors; 2) examine the associations between the stroke survivors’ QoL trajectories and caregivers’ anxiety, depression and burden over time. Methods: A longitudinal, multicentre study was conducted. A sample of 415 stroke survivors and their caregivers, after the stroke survivors’ discharge from rehabilitation hospitals, were enrolled. Stroke Impact Scale (SIS) 3.0 was used to assess the QOL of the stroke survivor. Caregiver trajectories for anxiety and depression were assessed with the Hospital Anxiety Depression Scale (HADS) while caregiver burden with Caregiver Burden Inventory (CBI). The Latent Class Growth Analyses (LCGA) were used to define the trajectories of the dimensions of the QOL. Results: Stroke survivors had similar trajectories on physical QOL dimensions. Differently, for SIS communication, emotional and memory dimensions, we identified two distinct trajectories. The first trajectory, representing 86% of survivors, included those who started with higher QOL levels and improved slightly to markedly in all psychological domains, with this improvement decelerating over time. The second trajectory (14% of survivors) included those who started with low overall levels of psychological QoL and experienced linear worsening of Memory and Communication, starting in the third month, and no change in Emotion and Participation. Caregivers of those patients in the second class experienced worse anxiety, depression and burden over time, compared to caregivers of patients in the first one. Conclusions: Our results identified several important risk factors for specific survival patterns that reinforce the need for more tailored interventions in order to improve stroke survivors’ QOL and consequently the caregiver anxiety, depression and burden. This requires a shift from a stroke survivor-centered approach to a stroke survivor and caregiver-centered approach.